Drug development has been hampered because it relies on the use of animal models that are costly, labor-intensive, time-consuming and questionable ethically.1 Of even greater concern is that animal models often do not predict results obtained in humans,2-3 and this is a particular problem when addressing challenges relating to metabolism, transport, and oral absorption of drugs and nutrients.4-5 For these reasons, there has been increasing interest in development of in vitro models of human intestinal function, including cell culture systems that utilize Transwell filter inserts6-7 which enable trans-epithelial barrier and transport studies,8-9 and miniaturized microfluidic models that also support long-term culture.10-14 Others have attempted to recreate the normal three-dimensional (3D) architecture of the intestinal lining in vitro by culturing human intestinal epithelial (e.g. Caco-2) cells on hydrogel substrates that were microengineered to mimic the shape, size and density of human intestinal villi.11 However, none of the existing in vitro intestinal models recapitulate the mechanically active microenvironment of living intestine (peristaltic motions and intralumenal fluid flow) that is critical for normal organ physiology,15 as well as for development of Crohn's disease and other intestinal disorders.16-17 Another limitation of existing in vitro gut models is that it has not been possible to grow living microbes on the luminal surface of cultured intestinal epithelium for extended periods as normally occurs in living intestine. This is a key problem because microbial symbionts normally contribute significantly to intestinal barrier function, metabolism and absorption of drugs and chemicals, and to many diseases.18-22 Development of an in vitro living cell-based model of the intestine that mimics the mechanical, structural, absorptive, transport and pathophysiological properties of the human gut along with its crucial microbial symbionts could accelerate pharmaceutical development, and potentially replace animal testing.